Synthesis of Well-Defined Phthalimide Monofunctional Hyperbranched Polyglycerols and Its Transformation to Various Conjugation Relevant Functionalities Gyö rgy Kasza,* ,† Gergely Kali, § Attila Domja ́ n, ‡ Lilla Pethő , ∥ Gyö rgyi Szarka, † and Be ́ la Iva ́ n* ,† † Polymer Chemistry Research Group, Institute of Materials and Environmental Chemistry and ‡ NMR Laboratory, Research Centre for Natural Sciences, Hungarian Academy, Magyar tudó sok kö rú tja 2, H-1117 Budapest, Hungary § Organic Macromolecular Chemistry, Saarland University, Campus C4.2, 166123 Saarbrü cken, Germany ∥ MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Pa ́ zma ́ ny Pe ́ ter se ́ ta ́ ny 1/A, H-1117 Budapest, Hungary * S Supporting Information ABSTRACT: Phthalimide monofunctional hyperbranched poly- glycerols (HbPG) were successfully synthesized, for the first time, by applying a new, highly efficient phthalimide/potassium phthalimide (PhthIm/K-PhthIm) initiating system for the anionic ring-opening multibranching polymerization of glycidol. As the analyses of the resulting polymers by UV and NMR spectroscopies, vapor pressure osmometry, aqueous and organic phase GPCs and ESI-MS proved, well-defined HbPGs with one phthalimide moiety, predetermined average molar masses, and narrow molar mass distributions were formed. The phthaloyl group was quantitatively cleaved by hydrazinolysis to form a monoamine functional HbPG. The amine functionality of the HbPG molecules at the initiating site was transformed into carboxylic, maleimide, and chloroacetamide groups. All functionalization reactions were quantitative as proved by multidimensional NMR spectroscopy. These findings indicate that the PhthIm/K- PhthIm combination can be utilized in the polymerization and subsequent derivatizations of other epoxides as well. In addition, the selectively modifiable reactive headgroup can be applied for obtaining various novel functionalized materials. ■ INTRODUCTION Hyperbranched polymers possessing relatively high branching densities and multiple terminal and/or pendant functionalities have been among the most intensively investigated macro- molecular assemblies during the past decades. 1−10 Their unique properties, for example, low solution/melt viscosity, compact volume, and high solubility compared to their linear analogues as well as the large number of functionalities per molecule make them attractive for common, specialty, and high added value applications in several fields. Such highly branched polymers are very promising candidates as components of a variety of advanced materials, e.g., specialty coatings, nanostructures, nanocomposites, smart materials, and delivery systems for bioactive molecules, such as drugs, nucleic acids, proteins, and enzymes, etc. 1−16 Undoubtedly, hyperbranched polyglycerol (HbPG) is one of the most attractive highly branched polymers for such purposes. HbPG is a polyether polyol which contains a large number of secondary and primary hydroxyl groups. 11−19 In addition to its outstanding water solubility and approved biocompatibility (blood compatible, nonimmunogenic, non- toxic), 13−16 the simple and modular synthesis of HbPG is also among the useful advantages of this polymer. Ring-opening multibranching polymerization (ROMBP) of glycidol results in well-defined structure and predetermined average molar mass. 17,18 Nowadays, based on the above-mentioned advanta- geous properties, HbPG is also intensively investigated as biocompatible nanocarrier. This highly branched polymer has also been recommended to replace poly(ethylene glycol) (PEG) in various application fields. 13,19,20 In the case of the linear PEG, several mono- and homo- or heterobifunctional derivatives with terminal functionalities have already been produced, and most of these are commercially available materials as well. End-functional PEGs with amine, carboxyl, maleimide, azide, alkyne, etc., end groups have been successfully applied in various conjugation reactions, called PEGylation, to produce stable biomaterials and drug delivery systems. 21,22 The main advantage of HbPG, compared to PEG, in addition to the known disadvantages of this linear polymer, 20 is related to the favorable physical and/or chemical properties of the hyperbranched polymer, which can be further tuned by derivatization of the high number of its hydroxyl function- alities. 23 By copolymerization of glycidol with other monomers or transformation of the hydroxyl groups of HbPG, multifunc- tional hyperbranched macromolecules with various terminal Received: February 24, 2017 Revised: April 3, 2017 Article pubs.acs.org/Macromolecules © XXXX American Chemical Society A DOI: 10.1021/acs.macromol.7b00413 Macromolecules XXXX, XXX, XXX−XXX